The specific objectives of this research proposal include: 1) clarification of the initial mechanisms and sequence of loss of compensatory vascular smooth muscle (VSM) tone that occurs during prolonged hemorrhagic hypotensive stress; 2) measurement of changes in the neural, humoral and ionic control of VSM tension underlying such loss; 3) a comparative study of differences in reactivity to circulatory stress of arterial and venous VSM in animals with normal and inherently elevated sympathetic activity. Normotensive and spontaneously hypertensive rats will be subjected to a period of prolonged hemorrhagic hypotension using the constant arterial pressure (35 mm Hg) and the normovolemic hypotensive models. An in situ intestinal mesenteric loop with intact neural and circulatory input will be placed in a semi-circular suffusion chamber capable of controlling temperature and suffusion rate. All measurements will be performed on the small intestinal mesenteric arteries (150-250 micron M) and small intestinal mesenteric veins (300-450 micron M). VSM properties and variables affecting VSM tension that will be measured in vivo in these vessels during hypotension include: 1) VSM transmembrane potentials (Em) and possible electrical activity; 2) VSM reactivity and sensitivity to perivascular neural stimulation (via changes in Em, blood vessel diameters and intraluminal pressure), to glucocorticoid administration, to suffusion with catecholamines, neural and VSM membrane blocking agents (e.g., tetrodotoxin, ouabain), ions (e.g., K ion, Ca 2 ion) and Ca 2 ion blockers (e.g., tetracaine and verapamil); 3) endogenous sympathetic efferent activity to VSM; 4) tissue and plasma catecholamines, K ion and Ca 2 ion. Such measurements should help clarify the mechanism and sequence of failure of the neurogenic, humoral and related ionic control mechanisms underlying control of VSM during prolonged circulatory stress. They should also shed light on the protective mechanisms of action of steroids in circulatory stress at the level of the VSM cell membrane.